Inherited long telomeres induce a genome-wide transcriptional response in budding yeast

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ID: 319525
2026
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Abstract
Eukaryotes typically maintain telomere length within a defined range. While short telomeres are known to activate DNA damage responses and limit cell proliferation, long telomeres are associated with extended proliferative capacity. The broader cellular consequences of long telomeres are comparatively less well understood. In budding yeast Saccharomyces cerevisiae, long telomeres have been shown to influence gene expression at specific loci, but whether long telomeres affect transcription genome-wide has not been reported. Here, we analysed transcriptomes in a lineage that inherited long telomeres (originally due to a rif2Δ mutation). Transcriptomes were assessed over two rounds of mitosis and meiosis in the absence of the rif2Δ mutation. We show that strains with long telomeres exhibit a distinct gene expression profile, including upregulation of membrane transporters and downregulation of a smaller subset of genes. Both up- and down-regulated genes were distributed across the genome, arguing against a purely telomereproximal effect on gene expression. Affected genes were enriched for Rap1 binding sites, consistent with a model in which long telomeres sequester telomereassociated transcriptional regulators, such as Rap1, and thereby affect gene expression at non-telomeric binding sites for these regulators. Accordingly, the magnitude of transcriptional changes was greatest in strains with the longest telomeres. Together, our findings demonstrate that long telomeres induce a genomewide transcriptional response that can accompany inherited long telomeres across generations. Similar effects of long telomeres are likely to occur in other eukaryotes, including humans, where long telomeres are associated with disease.
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openalex_W7167205662 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Vasilisa Sidarava, David Lydall
Journal current genetics
Year 2026
DOI
10.1093/genetics/iyag174
URL
https://doi.org/10.1093/genetics/iyag174
Keywords Keywords not found

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